PROJECT SUMMARY Extensive research has elucidated the function and structure of adult human visual cortex. However, the developmental mechanisms of human visual cortex are largely unknown for two main reasons. First, there is a paucity of macro-and micro-anatomical data on human brain development outside primary visual cortex (area V1). Second, prior microstructural research on brain development has been done mostly in animal models, but these models are inadequate for elucidating the development of human visual cortex, which has structures that do not exist in other mammals and shows a more protracted development than other species. To address this glaring gap in knowledge, we propose a groundbreaking research project that will generate an exciting, new collaboration between the Grill-Spector lab at Stanford University, who is expert in pediatric in vivo neuroimaging and the Paredes lab at UCSF, who is expert in human pediatric histology and stereology in postmortem brain tissue. Here, we propose to measure the structural development of human visual cortex during infancy using neuroimaging and immunohistochemistry (IHC) methods. The former will use noninvasive neuroimaging to determine macrostructural development of visual cortex longitudinally over 3 timepoints during the first year of life. The latter will use IHC and stereology in postmortem infant brains to elucidate how cellular populations and their microstructures develop. We propose to focus on primary visual cortex (V1), as well as face- and place-selective regions as they (i) can be identified within individual brains from macroanatomical landmarks alone, (ii) are located in different cytoarchitectonic regions, and (iii) show differential development: V1 matures first and face-selective regions last. In Aim 1, we will measure in vivo structural development of visual cortex in infants. Using innovations in quantitative magnetic resonance imaging (qMRI) and diffusion magnetic resonance imaging (dMRI) we will measure for the first time in vivo structural development of primary visual cortex (V1) and high-level visual cortex (face- and place-selective regions) during 3 timepoints in the first year of life (2, 7, and 12 months). In Aim 2, we will quantitatively measure cellular and microstructural development of human visual cortex. Using IHC, we will examine the development of cell types (neurons, astrocytes, oligodendrocytes) and cellular structures (arborization, synapses, and myelin) of infant brain samples that include the calcarine sulcus (where V1 resides), FG (where face-selective regions reside), and CoS (where place-selective regions reside). We will test if the same microstructural mechanisms occur in V1 and high-level visual cortex and produce models from IHC data to relate to neuroimaging data in Aim 1. The proposed research will provide key data that will fill significant gaps in knowledge on visual cortex development, and will pave a new, cutting-edge methodology for quantitative, ground-truth measurements of cortical microstructure in infants. The outcome of our research has important implications for developing non- invasive biomarkers of typical and atypical brain development.